The results demonstrate alpha2 modulation of NMDA receptor function as an important mechanism for neuroprotection. These results suggest a new therapeutic approach based on neuromodulation, instead of direct inhibition, of the NMDA receptor for the treatment of glaucoma and other CNS disorders associated with NMDA receptor overactivation.

The electroretinogram (ERG) oscillatory potential (OP) is a high-frequency, low-amplitude potential that is superimposed on the rising phase of the b-wave. It provides noninvasive evaluation of inner retina function in vivo and is a useful tool in basic research as well as in the clinic. While the OP is widely believed to be generated mainly by activity of the inner retina, the exact underlying neural mechanisms are not well understood. We have investigated the retinal mechanisms that underlie OP generation in Dutch-belted rabbits. The OP was isolated by band-filtering (100-1000 Hz) ERG signals. We used pharmacological agents that block specific transmitter receptors or voltage-gated channels in order to examine contributions of various retinal mechanisms to OP generation. Our results show that the OP elicited by a bright brief flash can be classified into early, intermediate, and late subgroups that are likely generated mainly by photoreceptors, action-potential-independent, and action-potential-dependent mechanisms in the ON pathway of the inner retina, respectively. ON bipolar cells themselves make only a small direct contribution to OP generation, as do horizontal cells and neurons in the OFF pathway.

Systemic treatment with memantine, a compound which does not lower intraocular pressure, was both safe and effective for reduction of functional loss associated with experimental glaucoma.

Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.

SUMMARY1. The spatial properties of rods, horizontal cells and bipolar cells were studied by intracellular recording in the isolated, perfused retina of the tiger salamander, Ambystoma tigrinum. Low stimulus intensities were used in order to keep cell responses close to, or within, their linear intensity/response range.2. Spatial properties of bipolar cell receptive fields, measured while perfusing with normal Ringer solution, were compared with those measured during exposure to agents that eliminated the bipolar cells' receptive field surround (RFS). In this way, the spatial properties of the receptive field centre (RFC) and those of the RFS could be characterized independently.3. To a good approximation, the contribution to the horizontal cell's response of unit area of its receptive field declined exponentially with distance from the centre of the receptive field. The (apparent) length constant describing this decay was 200 ,um. The one-dimensional length constant of the horizontal cell syncytium was thus 248 ,tm. The variation of response amplitude with the radius of a centred circular stimulus was consistent with this finding.4. This was true also of the RFCs of bipolar cells. The one-dimensional length constant of the RFC of off-centre bipolar cells averaged 124 ,um. That of the RFC of on-centre cells averaged 62 ,tm though values were more variable, the RFCs of some on-centre cells being comparable to those of off-centre cells. These values were independent of the class of photoreceptor driving the bipolar cell.5. The large size of the RFCs of off-centre cells and many on-centre cells cannot be explained by light scatter within the retina or by voltage spread within the rod syncytium. We proposed that off-centre cells are tightly coupled in a syncytium. Oncentre cells, on average, are less tightly coupled.6. The spatial properties of the bipolar cell's RFS were consistent with the notion that the RFS represents a convolution of the horizontal cell's receptive field and the bipolar cell's RFC.7. The spatial properties of bipolar cell receptive fields were reconstructed from the measured properties of their RFCs and the measured properties of horizontal cell receptive fields. Under the conditions of our experiments, the bipolar cell's response MS 7478 W. A. HARE AND W. G. OWEN could be described by a linear difference between a component generated by the RFC and a component generated by the RFS.8. The spatial filtering characteristics of the bipolar cells were calculated from our data. They show that, under the conditions of our experiments, bipolar cell receptive fields act as bandpass spatial filters tuned to an optimum spatial frequency of 0-8 mm-' (average for off-centre cells) and 1-02 mm-1 (average for off-centre cells).